Author: K. Ketchum Date: July 2015

Transcription

1 Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon Phone Fax Research Questions: What is the general utilization trend of the platelet inhibitor class since implementation of the clinical prior authorization (PA) in April 2012? How many patients encountering a PA for a platelet inhibitor drug do not continue on any antiplatelet therapy? What is the extent and length of concurrent dual antiplatelet therapy (DAPT) and does it conform to treatment guidelines? Conclusions: The preferred drugs, aspirin (70.3%) and clopidogrel (28.1%) were associated with the majority of patient index events. There were no discernable utilization trends temporal to the implementation of the clinical prior authorization criteria in April Very few patients encountered the clinical PA (n=19 patients, 1.5%) in the 21 months evaluated. Five patients (26% of those encountering the PA) did not get appropriate antiplatelet therapy within 30 days. Only 5 patients of the 19 had prior authorization requests (all approved). The remaining patients transitioned to coordinating care organizations (CCO) (n=5) or were switched to clopidogrel (n=4). Delayed care appears linked to hospitalization or transitioning to CCOs. There was a low overall rate (n=50, 4.0%) of DAPT utilization. This could be because there was cash payment for aspirin that is not captured in this evaluation. There was anecdotal evidence of the PA contributing to 1 patient not getting appropriate DAPT. Three patients were on inappropriate DAPT (Aggrenox with additional aspirin or clopidogrel). Just over half (56%) of DAPT patients had supporting diagnoses, leaving just under half that did not have supporting diagnoses. Most patients were on DAPT for 6 months or less. 1 Recommendations: Continue the PA policy with minor modifications (Appendix 1) that are consistent with updated treatment guidelines. Implement a retrospective safety net program to identify patients that do not start antiplatelet therapy within 14 days for additional transition assistance with a focus on insuring patients qualifying for DAPT are not discontinued prematurely. Author: K. Ketchum Date: July 2015

2 Background: The platelet inhibitor class ranks 35 th by net cost ($74,850) during quarter for the Oregon Health Plan (OHP) fee for service (FFS) program. 1 The platelet inhibitor drug class was added to the OHP Preferred Drug List on January 1, Non preferred drugs required only a funded diagnosis for approval. Additional clinical criteria for prasugrel and ticagrelor were implemented April 9, and upon market entry for vorapaxar. 4 Aspirin, clopidogrel, dipyridamole and aspirin/dipyridamole have been the preferred drugs since adding the class and now comprise 99% of market share. 1 Concern has been raised about prior authorization policies for platelet inhibitor drugs delaying access to drugs and subsequently contributing to increased cardiovascular events. 5 In the previous policy evaluations of combination inhalers for asthma 6 and anticoagulants 7 it was reported that only about a third of patients encountering a PA requirement subsequently had one requested for them by their clinician. Many patients were prescribed the desired alternative therapies but a significant subset of patients in both prior policy evaluations were appreciably delayed in getting needed medication or did not get it at all. In response to these findings, the anticoagulant PA policy was discontinued 8 and a retrospective safety net program was created for the combination inhalers. 9 As noted in the accompanying antiplatelet class review, 10 the recommendations for dual platelet inhibitor therapy (DAPT) is evolving for drug eluting stents. DAPT is recommended for 1 year in most patients receiving a drug eluting stent. DAPT is considered up to 30 months for patients at high risk for cardiovascular events and less than 6 months for patients at high risk of bleeding. The current recommendations are summarized below: Indication Dual DAPT Length Source secondary ACS or PCI with stent At least 12 months for ACS & drug eluting stent / 1 12 months bare metal stent ACCF/AHA secondary stroke prevention Not generally recommended (90 days maximum) AHA/ASA PAD Not recommended ACCF/AHA primary CVD prevention Not recommended ACC/AHA; ADA 2 The purpose of this policy evaluation is to document the general utilization trend of the platelet inhibitor class since implementation of the clinical PA in April 2012, quantify the number of patients encountering a PA that do not continue any drug therapy and describe current DAPT to inform drug policy proposals. Methods: Patients were included if they had a paid FFS drug claim for any drug in Table 1 or a denied fee for service (FFS) drug claim with Explanation of Benefit (EOB) code 1056 (i.e. PA Required ) and simultaneously no EOB of 2017 (i.e. Patient enrolled in MCO ) from April 2012 and through March Patients were excluded if they had Medicare Part D coverage as indicated by benefit packages of BMM or BMD. Patients were also excluded if they had aspirin monotherapy that consisted of claims of less than 28 Days Supply or daily unit consumption equivalent to 80 mg (0.75 units 2.25 units) to 325 mg per day (0.5 units to 1.25 units). Daily unit consumption is equal to quantity dispensed / days supply. Using only FFS claims, the first platelet inhibitor paid or denied claim per patient during the study period was designated the index event. If patients had both a paid claim and a denied claim, they were counted in the paid claim category and

3 their denied claim was ignored. Patients were excluded if they had less than 75% days of combined FFS or coordinated care organization eligibility for the 12 months after the index event. Table 1. Platelet inhibitor Drugs PDL HSN GSN Brand Generic N TICLOPIDINE HCL TICLOPIDINE HCL Y AGGRENOX ASPIRIN/DIPYRIDAMOLE Y PLAVIX CLOPIDOGREL BISULFATE Y PLAVIX CLOPIDOGREL BISULFATE N EFFIENT PRASUGREL HCL N EFFIENT PRASUGREL HCL N BRILINTA TICAGRELOR N ZONTIVITY VORAPAXAR SULFATE Y ASPIRIN ASPIRIN 325 mg Y CHILDREN'S ASPIRIN ASPIRIN 81 mg Y ASPIRIN EC ASPIRIN 325 mg Y LOW DOSE ASPIRIN EC ASPIRIN 81 mg HSN = hierarchical ingredient code list (HICL) sequence number as reported by First DataBank Patients were categorized by whether the index event was a paid or denied claim. Patients were also categorized by the generic drug name of index event. Patients with paid index events were categorized in the following groups: 1) New platelet inhibitor start no paid FFS or encounter platelet inhibitor claims within 102 days prior to index event. 2) Continuation Therapy Patients where the index event is for the same hierarchical ingredient code list sequence number (HSN) as a paid FFS or encounter platelet inhibitor claim within 102 days prior. 3) Other Index event does not fit in prior categories. Patients with denied index events were categorized in the following groups to describe drug therapy disruption: 1) Platelet inhibitor drug < 14 days 2) Platelet inhibitor drug > 14 and < 90 days 3) Platelet inhibitor drug > 90 days or no platelet inhibitor claims 3 Platelet inhibitor therapy length was determined for each HSN using the date of the first paid claim and last paid claim plus Days Supply entry with a minimum therapy gap in therapy of 7 days. Patients with a minimum of concurrent therapy of 60 days with overlapping therapy of 2 or more HSNs were included in the DAPT analysis. Length of concurrent therapy length was determined as the length in days from the date of last overlapping span minus the date of the first overlapping span. Patients were flagged if they had one of the selected diagnosis code (Table 6) on any paid FFS or encounter claim from 1 year prior to 1 month after the index event.

4 Results: Figure 1 displays the number of patients per 10,000 members per month on each of the platelet inhibitor drugs. This chart does not distinguish daily aspirin use for antiplatelet effect from use for pain. Aspirin dominates the class and the gross number of patients is quite constant averaging 2677 ( ) patients per month. The variation in trend is primarily due to enrollment fluctuations, notably the large influx of covered lives in January Clopidogrel averages 98 (66 121) patients per month and prasugrel averages 4 (0 8) patients per month. There was one unique patient on ticagrelor during the entire 2 years. Figure 1 Unique Utilizing Members per Fee For Service Members (x10000) Aspirin Clopidogrel Bisulfate Aspirin/Dipyridamole Ticagrelor Prasugrel Clinical criteria for nonpreferred drugs implemented April Jan-12 Feb-12 Mar-12 Apr-12 May-12 Jun-12 Jul-12 Aug-12 Sep-12 Oct-12 Nov-12 Dec-12 Jan-13 Feb-13 Mar-13 Apr-13 May-13 Jun-13 Jul-13 Aug-13 Sep-13 Oct-13 Nov-13 Dec-13 Jan-14 Feb-14 Mar-14 Apr-14 May-14 Jun-14 Jul-14 Aug-14 Sep-14 Oct-14 Nov-14 Dec-14

5 Table 2 displays the demographics of all patients with a FFS claim and where aspirin users were restricted to those on a daily dose of mg per day. The study population also met the minimum eligibility requirements. The study population is very similar in demographics to those that do not meet the eligibility requirements. It is almost exclusively mid aged adults, both genders are represented equally and about 33% are non white. Table 2 - Demographics All Patients Study with FFS Claim Population N= 1,365 % 1,230 % Mean age (range) 53.1 (0-89) 53.3 (0-89) < % % , % 1, % > % % Female % % White % % Table 3 displays the type of index event. Only 1.8% of patients had denied index events indicating the preferred platelet inhibitors are prescribed predominately and relatively few patients encountered the prior authorization requirement. 5 Table 3 - Platelet inhibitor Index Therapy Type All Patients Study with FFS Claim Population N= 1,365 % 1,230 % Denied % % Paid New Start % % Paid Continuation of Same Therapy % % Table 4 displays the index events by drug. Preferred drugs account for 99.5% of paid index events. No patients were prescribed ticlopidine or vorapaxar. Six patients with paid index events had continued on prasugrel from the period prior to the clinical PA criteria being implemented. There were 22 patients with denied index events. Three of 22 patients were prescribed preferred drugs (1 clopidogrel, 2 aspirin) and encountered a PA requirement because the dispensing pharmacy used a Dispense As Written (DAW) code of 1 which overrides the generic pricing. One aspirin patient (a

6 diabetic with no cardiac indications) subsequently got it paid for by a CCO the next day; the other aspirin patient had no apparent indication for antiplatelet therapy and did not ever have a subsequent claim for it; and the clopidogrel patient had no record of any paid drug claims and further investigation determined the patient had external drug coverage. Nineteen of 22 patients were prescribed non preferred drugs (18 prasugrel, 1 ticagrelor). Only 6 of the 19 patients had claims for any platelet inhibitor within 14 days (average of 7 days). Of these, 2 were switched to clopidogrel, 2 got prasugrel and the other ticagrelor. The last patient was already on aspirin when denied prasugrel and then eventually was switched to clopidogrel 150 days latter. This patient underwent a coronary bypass, was a diabetic, and also had atrial fibrillation and mitral valve disorder and qualified for DAPT. Nine of the remaining 13 patients with denied prasugrel index events had subsequent claims between 14 and 90 days (average 30 days). A manual review of these patients found 5 patients transitioned to CCOs where 4 had subsequent claims for prasugrel and 1 was switched to clopidogrel. Of the remaining 4 FFS patients, 3 got prasugrel and 1 clopidogrel. All 9 patients who had delayed antiplatelet therapy had indications of stent placement, bypass surgery or myocardial infarction. None were on dual antiplatelet therapy but all also had concurrent nonsteroidal therapy, corticosteroid therapy or antiulcer therapy so may have been at higher risk of bleeding. Six patients did not have a claim for platelet inhibitors within 90 days. Two mentioned above, encountered PA for DAW 1. Of the remaining 4, 1 had no apparent indication for antiplatelet therapy other than primary cardiovascular event prevention and was started on aspirin 3 months after the denied index and the remaining 3 patients had compelling cardiac indications. Two patients eventually started daily aspirin more than a year after the denied index event and one had no record of antiplatelet therapy. In summary, 14 of 22 patients with denied index events got appropriate antiplatelet therapy within 30 days, 2 had no apparent indication for antiplatelet therapy, 1 had other insurance for drug coverage and 5 patients did not receive appropriate antiplatelet therapy within 30 days or ever. 6 Table 4 - Drug Distribution of Study Population Denied Index Events Total Paid Total Denied by subsequent paid platelet inhibitor claim Index Events Index Events <=14 Days >14 & <90 Days >=90 Days or Never N= 1,208 % 22 % % % 6# 27.3% TICLOPIDINE HCL ASPIRIN/DIPYRIDAMOLE % CLOPIDOGREL BISULFATE % 1* 4.5% 2 9.1% 2 9.1% PRASUGREL HCL 6 0.5% % 2 9.1% % TICAGRELOR 1^ 4.5% 1^ 4.5% VORAPAXAR SULFATE ASPIRIN % 2* 9.1% 1*+1 9.1% % *patients with Dispense As Written (DAW) 1 index; = patients with denied prasugrel index; ^ = patient with denied ticagrelor index; #= 3 patients had no subsequent antiplatelet claims

7 Table 5 displays patients on a minimum of 60 days of concurrent platelet inhibitor. Only 50 of 1230 (4.0%) patients included in the study were on DAPT. The vast majority (n=46, 92%) were on aspirin and clopidogrel for an average of 188 days (about 6 months). There were 30 (60%) on DAPT for 6 months or less and 21 (42%) were on DAPT for more than 6 months. Patients could have more than one concurrent span. If one span was longer than 6 months, they were placed in > 6 months group and removed from the < 6 months group. One patient was on aspirin and clopidogrel off and on for about 18 months and then aspirin and prasugrel for less than 6 months and is counted twice in Table 5. There are currently no recommendations for using the combination aspirin/dipyridamole with either aspirin (n=2) or clopidogrel (n=1). Table 5 - Study Population Concurrent Therapy by Drug Combination Concurrent therapy minimum of 60 days overlap in two years Concurrent Users Length of Overlap <= 6 months > 6 months Drug 1 Drug 2 50 % Mean Range % 21* 42.0% Aspirin Clopidogrel Bisulfate % % 20* 40.0% Aspirin Prasugrel 2 4.0% * 4.0% Aspirin Aspirin/Dipyridamole 2 4.0% % 1 2.0% Aspirin/Dipyridamole Clopidogrel Bisulfate 1 2.0% % * One patient was on aspirin and clopidogrel off and on for about 18 months and then aspirin and prasugrel for less than 6 months and is counted twice in Table 5. 7 Table 7 displays the selected diagnoses of interest associated with the 50 patients on DAPT. The majority (56%) had documented diagnoses suggesting secondary prevention for acute coronary syndrome and likely appropriate. Limitations: It is difficult to distinguish patients using aspirin for pain versus for antiplatelet therapy. Patients on aspirin monotherapy were restricted to those on daily aspirin doses of 80 mg to 325 mg. This may have under estimated the number of non compliant patients on aspirin monotherapy. However, if a patient had any other antiplatelet drug plus any aspirin dose, the aspirin was included for purposes of identifying potential DAPT. Despite this liberal definition, the number of patients on DAPT appears low. There remains a possibility that patients are paying cash for over the counter aspirin and could not be identified as DAPT. There was no attempt to associate diagnoses to antiplatelet monotherapy. In retrospect, this may have helped to verify the apparent low rate of DAPT but also added complexity and was not the focus of this evaluation. It has been reported that insurance coverage affects the type of stent used, with just 3.7% of those receiving drug eluting stents having Medicaid insurance, which again would limit length of DAPT to 6 months. 11 Additionally, the patients in this evaluation are generally younger and may not warrant long term therapy.

8 Anecdotally, the manual review of patients with delayed antiplatelet therapy identified one patient that was definitely appropriate for DAPT. The other manually reviewed patients had indicators of high risk of bleeding which may have precluded them from long term DAPT, but they were still appropriate for short term DAPT. Table 7: Diagnostic Distribution of All Patients with Dual Antiplatelet Therapy Each group mutually-exclusive in priority of 1, 2, 3, 4, 5 1 year Prior + Month After Index n=50 % 1) Secondary acute coronary syndrome prevention % 1. AMI 410xx % 2. Other acute & sub-acute forms of ischemic heart disease 411xx % 3. Angina 413xx % 4. Chest Pain 7865x % 2) Secondary stroke prevention % 1. Occlusion and stenosis of precerebral arteries 433xx 4 8.0% 2. Occlusion of cerebral arteries 434xx % 3. Transient cerebral ischemia 435xx 3 6.0% 4. Acute, but ill-defined, cerebrovascular disease 436xx % 5. Hemiplegia and hemiparesis 342xx 2 4.0% 6. Other paralytic syndromes 344xx 0.0% 3) Diagnoses indicating primary prevention % 1. Other forms of chronic ischemic heart disease 414xx % 2. Atherosclerosis 440xx 0.0% 3. Other peripheral vascular disease 443xx 1 2.0% 4. Arterial embolism and thrombosis 444xx 0.0% 5. Personal history of diseases of circulatory system V125xx 0.0% 4) Anticoagulant indications 0 0.0% 1. Cardiac dysrhythmias 427xx 0.0% 2. Other venous embolism and thrombosis 453xx 0.0% 3. Pulmonary embolism and infarction 4151x 0.0% 5) None of the above % 8

9 References: 1. Internal Report. OHP FFS Q Market Share Report (no 340b). April The OHP Preferred Drug List (PDL) An Overview. Or Health Plan. Accessed June 26, Oregon Medicaid PA Criteria, April Or Health Plan. April Accessed June 26, Oregon Medicaid PA Criteria, August Or Health Plan. August Accessed June 26, Jackevicius CA, Tu JV, Demers V, et al. Cardiovascular outcomes after a change in prescription policy for clopidogrel. N Engl J Med. 2008;359(17): Ketchum KL. Policy Evaluation: Step Therapy Prior Authorization of Combination Inhaled Corticosteroid / Long Acting Beta Agonists. Or State Univ Drug Use Res Manag. May Accessed June 26, Ketchum KL. Policy Evaluation: Prior Authorization of Non Preferred Oral Anticoagulants. Or State Univ Drug Use Res Manag. May Accessed June 26, Oregon Drug Use Review / Pharmacy & Therapeutics Committee Agenda Packet. Or State Univ Drug Use Res Manag Or Pharm Ther Comm Meet Agenda. May Accessed June 26, Oregon Drug Use Review / Pharmacy & Therapeutics Committe Meeting Minutes. Or State Univ Drug Use Res Manag. November Accessed June 26, Herink M. Antiplatelets Class Update. July policy/oregon pharmacy therapeutics committee/meetingsagenda. Accessed June 26, Gaglia MA, Torguson R, Xue Z, et al. Insurance Type Influences the Use of Drug Eluting Stents. JACC: Cardiovascular Interventions. 2010;3(7): doi: /j.jcin

10 Appendix 1: Platelet Inhibitor Prior Authorization Criteria Goal: Antiplatelets Approve antiplatelets for funded diagnoses which are supported by medical literature. Length of Authorization: Up to 12 months. Requires PA: Non-preferred drugs Covered Alternatives: Preferred alternatives listed at Approval Criteria 1. What diagnosis is being treated? Record ICD9 code Is the diagnosis an OHP funded diagnosis? Yes: Go to #3 No: Pass to RPh. Deny, not funded by the OHP. 3. Will the prescriber consider a change to a preferred product? Yes: Inform prescriber of preferred alternatives. 4. Is this continuation of hospital treatment? Yes: Approve for 30 days only and inform provider of preferred products. No: Go to #4 No: Go to #5

11 Approval Criteria 5. Is the request for either prasugrel or vorapaxar AND does the patient have a history of stroke, TIA or intracranial hemorrhage? Yes: Pass to RPh. Deny for medical appropriateness No: Approve for FDA-approved indications for up to 1 year. If vorapaxar is requested, it should be approved only when used in combination with aspirin and/or clopidogrel. There is limited experience with other platelet inhibitor drugs or as monotherapy. FDA Approved Indications (July 2015) 2 o 2 o 2 o ACS ASA/DP ER Stroke x PAD MI No PCI PCI 11 clopidogrel x x x x x prasugrel CI x ticagrelor x x vorapaxar CI x x Abbreviations: 2⁰ = secondary prevention; ACS=Acute Coronary Syndrome; ASA/DP ER = aspirin/dipyridamole; CI=contraindication; PCI=Percutaneous Intervention; X = FDA approved indication. P&T / DUR Review: 7/15 (KK); 11/11 Implementation: TBD; 7/31/14; 4/9/12